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DOI | 10.1126/science.aat9689 |
Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages | |
Greenwood, Daniel J.1; Dos Santos, Mariana Silva1; Huang, Song2; Russell, Matthew R. G.1; Collinson, Lucy M.1; MacRae, James I.1; West, Andy3; Jiang, Haibo2,4; Gutierrez, Maximiliano G.1 | |
2019-06-28 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6447页码:1279-+ |
文章类型 | Article |
语种 | 英语 |
国家 | England; Australia |
英文摘要 | Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis, remains the world's deadliest infectious disease. Sterilizing chemotherapy requires at least 6 months of multidrug therapy. Difficulty visualizing the subcellular localization of antibiotics in infected host cells means that it is unclear whether antibiotics penetrate all mycobacteria-containing compartments in the cell. Here, we combined correlated light, electron, and ion microscopy to image the distribution of bedaquiline in infected human macrophages at submicrometer resolution. Bedaquiline accumulated primarily in host cell lipid droplets, but heterogeneously in mycobacteria within a variety of intracellular compartments. Furthermore, lipid droplets did not sequester antibiotic but constituted a transferable reservoir that enhanced antibacterial efficacy. Thus, strong lipid binding facilitated drug trafficking by host organelles to an intracellular target during antimicrobial treatment. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000473271300047 |
WOS关键词 | MYCOBACTERIUM-TUBERCULOSIS ; BEDAQUILINE ; CELLS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201757 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Francis Crick Inst, London, England; 2.Univ Western Australia, Ctr Microscopy Characterisat & Anal, Perth, WA, Australia; 3.GlaxoSmithKline, Stevenage, Herts, England; 4.Univ Western Australia, Sch Mol Sci, Perth, WA, Australia |
推荐引用方式 GB/T 7714 | Greenwood, Daniel J.,Dos Santos, Mariana Silva,Huang, Song,et al. Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages[J]. SCIENCE,2019,364(6447):1279-+. |
APA | Greenwood, Daniel J..,Dos Santos, Mariana Silva.,Huang, Song.,Russell, Matthew R. G..,Collinson, Lucy M..,...&Gutierrez, Maximiliano G..(2019).Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages.SCIENCE,364(6447),1279-+. |
MLA | Greenwood, Daniel J.,et al."Subcellular antibiotic visualization reveals a dynamic drug reservoir in infected macrophages".SCIENCE 364.6447(2019):1279-+. |
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